Peter J. Ratcliffe

Sir Peter John Ratcliffe, FRS, FMedSci (born 14 May 1954) is a British Nobel Laureate physician-scientist who is trained as a nephrologist.[1][2][3] He was a practising clinician at the John Radcliffe Hospital, Oxford and Nuffield Professor of Clinical Medicine and head of the Nuffield Department of Clinical Medicine at the University of Oxford from 2004 to 2016. He has been a Fellow of Magdalen College, Oxford since 2004. In 2016 he became Clinical Research Director at the Francis Crick Institute,[4] retaining a position at Oxford as member of the Ludwig Institute of Cancer Research and Director of the Target Discovery Institute, University of Oxford.[5]

Sir

Peter J. Ratcliffe

FRS FMedSci
Ratcliffe in 2019
Born
Peter John Ratcliffe

(1954-05-14) 14 May 1954
Morecambe, England, UK
EducationLancaster Royal Grammar School, Gonville and Caius College, Cambridge (MB BChir, MD)
University of Oxford
St Bartholomew's Hospital Medical College
AwardsFellow of the Royal Society
Albert Lasker Award for Basic Medical Research
Physiological Society Annual Review Prize Lecture
Louis-Jeantet Prize for Medicine
Knight Bachelor
Fellow of the Academy of Medical Sciences
EMBO Membership
Baly Medal
Grand Prix scientifique de la Fondation Lefoulon-Delalande
Robert J. and Claire Pasarow Foundation Medical Research Award
Nobel Prize in Physiology or Medicine
Scientific career
InstitutionsFrancis Crick Institute
Nuffield Department of Population Health, University of Oxford
WebsiteOfficial website

Ratcliffe is best known for his work on cellular reactions to hypoxia, for which he shared the 2019 Nobel Prize in Physiology or Medicine with William Kaelin Jr. and Gregg L. Semenza.[6][7]

Education and training

Ratcliffe was born in Lancashire[8] on 14 May 1954, to William Ratcliffe and Alice Margaret Ratcliffe.[9] He attended Lancaster Royal Grammar School from 1965 to 1972.[10]

He won an open scholarship to Gonville and Caius College, Cambridge in 1972 to study Medicine at the University of Cambridge[11] and then completed his MB BChir medical degree with distinction at St Bartholomew's Hospital Medical College in 1978.[12]

Ratcliffe then trained in renal medicine at Oxford University, focusing on renal oxygenation.[13] He earned a higher MD degree from University of Cambridge in 1987.[14]

Career

In 1990, Ratcliffe received a Wellcome Trust Senior Fellowship to study cellular responses to hypoxia from low oxygen levels in the blood.[12][15] From 1992 to 2004 he was Senior Research Fellow in Clinical Medicine at Jesus College, Oxford.[16] In 2002, Ratcliffe was accepted into the Academy of Medical Sciences and was appointed the following year the Nuffield Professor and Head of the Nuffield Department of Clinical Medicine at Oxford.[17]

Research
Illustration of how cells sense and adapt to oxygen availability

In 1989, Ratcliffe established a laboratory in Oxford University's Nuffield Department of Medicine to explore the regulation of erythropoietin (EPO), a hormone released by the kidneys and responsible for stimulating the production of red blood cells. EPO was known to be produced by the kidneys in response to low oxygen levels, and Ratcliffe's work looked to understand the mechanisms of how the kidneys detected hypoxia (low oxygen levels in the blood) to trigger EPO production. From his studies, Ratcliffe discovered that the mRNA from kidneys that were part of the EPO production pathway that were capable of detecting hypoxia was also present in several other organs, both human and animal, including the spleen, brain, and testes.[18] His group found that cells from these organs could switch on EPO production when deprived of oxygen.[17] Further, Ratcliffe was able to modify other cells using the identified mRNA to give these cells oxygen-sensing capabilities.[18]

Building on these discoveries, the Ratcliffe group, along with joint studies with William Kaelin and Gregg Semenza, helped to uncover a detailed molecular chain of events that cells use to sense oxygen. A specific step identified was the binding of proteins expressed by the Von Hippel–Lindau tumor suppressor gene (VHL) to hypoxia-inducible factors (HIF), a transcription factor which trans-activates the EPO gene. Ratcliffe found that the VHL protein can bind a hydroxylated residues of HIF when oxygen is present at acceptable levels; the VHL protein then ubiquitylates the HIF protein which ultimately leads to the HIF protein's destruction. When oxygen levels fall, oxygen-requiring HIF hydroxylase enzymes, PHD1, 2 and 3 no longer act and VHL does not bind HIF, allowing HIF to remain and activate the EPO gene. This is a process that takes minutes to complete allowing the body to react quickly to hypoxia.[19]

This same pathway is also switched on in many cancer tumours, allowing them to create new blood vessels to sustain their growth. Much of the current understanding of hypoxia has emerged from the laboratory of Ratcliffe.[13] The understanding of the molecular pathway of EPO production from hypoxia has led to the development of drugs that block VHL from binding with HIF to help treat patients with anaemia and kidney failure.[19]

Personal life

Ratcliffe married Fiona Mary MacDougall in 1983.[9]

Selected honours and awards

Ratcliffe has received a number of awards, accolades, and honours for his seminal work on hypoxia.

He was knighted in the 2014 New Year Honours for services to clinical medicine.[26]

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References
  1. Peter Ratcliffe - Hypoxia Biology Laboratory - website of the Francis Crick Institute
  2. Biologists who decoded how cells sense oxygen win medicine Nobel - website of the scientific journal Nature
  3. Sir Peter Ratcliffe - website of the Hellenic Society of Biochemistry and Molecular Biology
  4. "Peter Ratcliffe | The Francis Crick Institute". The Francis Crick Institute. Retrieved 3 January 2018.
  5. "Peter Ratcliffe". Crick. Retrieved 8 October 2019.
  6. "The Nobel Prize in Physiology or Medicine 2019". NobelPrize.org. Retrieved 7 October 2019.
  7. Kolata, Gina; Specia, Megan (7 October 2019). "Nobel Prize in Medicine Awarded for Research on How Cells Manage Oxygen". The New York Times. Retrieved 8 October 2019.
  8. "Sir Peter J. Ratcliffe – Facts – 2019". The Nobel Prize. Nobel Media AB. Retrieved 8 October 2019.
  9. "Ratcliffe, Sir Peter (John)". Who's Who. A & C Black. doi:10.1093/ww/9780199540884.013.U43812. Retrieved 9 October 2019.
  10. Gayle Rouncivell (8 October 2019). "Former Lancaster Royal Grammar School pupil to be awarded Nobel Prize". The Francis Crick Institute. Retrieved 8 October 2019.
  11. "Cambridge alumnus Sir Peter Ratcliffe awarded 2019 Nobel Prize in Physiology or Medicine". University of Cambridge. 7 October 2019. Retrieved 8 October 2019.
  12. "Peter J. Ratcliffe". Gairdner. Retrieved 2 January 2014.
  13. "Sir Peter J Ratcliffe wins the Nobel Prize in Medicine 2019". University of Oxford. 7 October 2019. Retrieved 8 October 2019.
  14. "Peter Ratcliffe". The Francis Crick Institute. 7 October 2019. Retrieved 8 October 2019.
  15. "Professor Sir Peter Ratcliffe". Magdalen College. University of Oxford. Retrieved 9 October 2019.
  16. "Sir Peter J Ratcliffe wins the Nobel Prize in Medicine 2019". Jesus College. University of Oxford. Retrieved 7 November 2019.
  17. "Professor Sir Peter Ratcliffe to give this year's Linacre Lecture". St John's College Cambridge. 11 January 2018. Retrieved 9 October 2019.
  18. Hurst, Jillian H. (13 September 2016). "William Kaelin, Peter Ratcliffe, and Gregg Semenza receive the 2016 Albert Lasker Basic Medical Research Award". The Journal of Clinical Investigation. 126 (10): 3628–3638. doi:10.1172/JCI90055. ISSN 0021-9738. PMC 5096796. PMID 27620538. Further support for an oxygen-sensing mechanism was provided by the discovery of erythropoietin (EPO), a glycoprotein hormone that stimulates erythrocyte production [...] During the same time period in which Semenza was developing EPO-transgenic mice, Peter Ratcliffe, a physician and kidney specialist, was establishing a laboratory in Oxford University’s Nuffield Department of Medicine to study the regulation of EPO
  19. Ledford, Heidi; Callaway, Ewen (7 October 2019). "Biologists who decoded how cells sense oxygen win medicine Nobel". Nature. PMID 31595071. Retrieved 9 October 2019.
  20. "Wellcome Trust | Wellcome Trust". Wellcome.ac.uk. 26 March 2009. Archived from the original on 25 May 2013. Retrieved 2 January 2014.
  21. "Nuffield Department of Medicine - Prof Peter J Ratcliffe FRS". Ndm.ox.ac.uk. Retrieved 2 January 2014.
  22. Foundation, Lasker. "Oxygen sensing – an essential process for survival". The Lasker Foundation. Retrieved 7 October 2019.
  23. "Buchanan Medal". Royal Society. Retrieved 11 December 2017.
  24. "Massry Prize 2018 – Keck School of Medicine of USC". Retrieved 8 October 2019.
  25. "The Nobel Prize in Physiology or Medicine 2019". NobelPrize.org. Retrieved 8 October 2019.
  26. "No. 60728". The London Gazette (Supplement). 31 December 2013. p. 2.
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